Cutaneous melanoma is a serious human malignancy. Observations from several groups have established that ICAM-1 (CD54) expression on the surface on melanomas is associated with enhanced growth and metastatic potential, and, ultimately, with a poorer prognosis. In this P& F Study we will test the hypothesis that ICAM-1 expression is causally related to the increased growth and metastatic potential of melanomas cell line is stably trans-using antisense growth and metastatic potential of melanomas. This will be accomplished using antisense technology in which the murine B16 melanoma cell line is stably transfected with an episomal replication vector containing ICAM-1 cDNA in the antisense position. The B16 melanoma cell line is particularly well-suited for this purpose because it constitutively expresses cell surface ICAM-1 and it metastasizes widely. Initial experimentation will be designed to construct an antisense ICAM-1 episomal vector that can be used for stable transfection into murine cell lines. Once this has been accomplished, the plasmid will be transfected into the B16 melanoma tumor line. Its effects on ICAM-1 protein expression will then be examined by flow cytometry. Comparison will be made to nontransfected cells to cells transfected with a control plasmid lacking the anti-ICAM-1 transfected cell line will then be evaluated using in vitro immunological assays in which ICAM-1 expression is thought to be important. Finally, the in vivo consequences of antisense ICAM-1 RNA transfection will be appraised. Antisense transfected cells will be transplanted to C57B1/6 mice and their growth and metastatic potential will be assessed. The results thus generated should provide new information regarding the role of ICAM-1 in the immunopathogenesis of melanoma.